Sleep Fragmentation, Astroglial Activation, and Cognitive Impairment in Older Adults

Alzheimer’s Disease (AD) and other dementias are a growing public health concern. Emerging evidence suggests that sleep disruption may contribute to the risk of dementia. In model organisms, sleep disruption can lead to astrocyte activation and impaired cognition. However, whether this is true in older humans is uncertain. We tested the hypothesis that sleep fragmentation is associated with astrocyte activation and downstream cognitive impairment. We used published human single nucleus RNA-seq data to identify marker genes for human activated astrocytes, and quantified the expression of these genes from bulk RNA-seq of dorsolateral prefrontal cortex tissue from 1080 older adults. We related this to antemortem sleep fragmentation measured by actigraphy and to cognitive function. Greater sleep fragmentation was associated with greater expression of activated astrocyte marker genes, which was in turn associated with worse cognition. This is compatible with the hypothesis that astrocyte activation may link sleep fragmentation to cognitive impairment.M.Sc